Magnetic Resonance Imaging (MRI) has become a standard diagnostic tool with extensive clinical applications. Paramagnetic contrast agents are used to enhance the water proton relaxivity in specific tissues in about a third of clinical MRI protocols. The most clinically widespread contrasts are based on complexes of the gadolinium (III) ion which has a very high electronic spin (S=7/2) per ion. In the last ten years, considerable progress has been made in the design of Gd(III) contrasts and attention has recently turned to the detailed characterization of the magnetic properties of these complexes. Transition metal-based contrasts have been less well developed and offer a number of possibilities for new contrast agents. Compared to the gadolinium-based complexes, transition metal contrast agents should offer decreased toxicity, greater flexibility in ligand design, better control over the geometry of the site and the number of coordinated water molecules, and a lower cost. The electronic and geometrical factors that affect the relaxivities of transition metal complexes are, however, not well defined. Theoretical models of relaxation processes suggest that the magnitude of the electronic spin and its spatial distribution, the rate of water exchange, the number of coordinated waters, and the hydrogen-bonding capacities of the complexes play major roles in determining their properties as MRI contrast agents. The goals of this proposal are to examine in detail the relaxometry of a systematically varied series of Cu(II) complexes of polyamine macrocycles to define more clearly how chemical factors affect the relaxivities. Copper(II) is ideal for these studies since established synthetic procedures and structural characterizations are available for a large number of the complexes. The goals are to understand how relaxivities vary with 1) the number of potential water coordination sites and the water exchange rates, 2) the extent of hydrogen-bonding interactions with the solvent, and 3) delocalization of the unpaired spin density. The results of these studies will be generalizable to other transition metal-based systems.